Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

Xiaojun Li; Elena E. Giorgi; Manukumar Honnayakanahalli Marichann; Brian Foley; Chuan Xiao; Xiang-peng Kong; Yue Chen; Bette Korber; Feng Gao

Pan_SL-CoV sequences are generally more similar to SARS-CoV-2 than CoV sequences, other than RaTG13 and ZXC21, but are more divergent from SARS-CoV-2 at two regions in particular: the beginning of the ORF1b gene and the highly divergent N terminus of the S gene (regions 3 and 4, respectively, fig. 1A ). Within-region phylogenetic reconstructions show that Pan_SL-CoV sequences become as divergent as BtKY72 and BM48-31 in region 3 ( fig. 1D ), while less divergent in region 4, where Pan_SL-CoV_GD clusters with ZXC21 and ZC45 (fig . 1E ). Together, these observations suggest ancestral cross-species recombination between pangolin and bat CoVs in the evolution of SARS-CoV-2 at the ORF1a and S genes. Furthermore the discordant phylogenetic clustering at various regions of the genome among clade 2 CoVs also supports extensive recombination among these viruses isolated from bats and pangolins.